1. Field of the Invention:
The present invention relates to an improved process for producing steroidal compounds by converting a steroidal 10-methyl-1, 4-dien-3-one to a steroidal 19-nor-3-hydroxy-1,3,5(10)-triene.
2. Description of the Prior Art:
The steroidal 19-nor-3-hydroxy-1,3,5(10)-trienes produced by the process of the present invention, particularly 3-hydroxyestra-1,3,5(10)-trien-17-one (estrone) are useful as ovarian hormones and as intermediates for preparation of steroidal hormones such as ethisterone. Ethisterone is important as a main component of oral contraceptive pills.
It is known that estrone is produced by the pyrolysis of androst-1,4-dien-3, 17-dione which is one of the steroidal 10-methyl-1, 4-dien-3-ones.
There are also known processes wherein estrone is produced by feeding a solution of androst-1, 4-dien-3, 17-dione dissolved in decalin, tetralin, cyclohexane, a higher aliphatic hydrocarbon or mineral oil into a glass tower reactor having a length to diameter ratio of from 10 to 15, and optionally packed with glass, and thereafter pyrolyzing the solution. (J. Org. Chem., 15 292 (1950); J. Am. Chem. Soc., 72 4531 (1953); U.S. Pat. No. 2,594,349). However, such processes suffer from the significant disadvantage of low selectivity. Yields are only 40 - 60 percent. Another hindrance to the commercial development of such processes for the production of estrone is the difficulty in industrial production of providing sufficient heating surface to heat the reaction mixture to the reaction temperature. The low selectivity of these processes has been shown to arise from the thermal instabilities of androst-1, 4-dien-3, 17-dione and estrone.
Through studying the high temperature stability of these compounds it has been found that unnecessarily prolonged heating at temperatures above 300.degree. C will result in an increase in the amount of unfavorable by-products. On the other hand, the compounds are stable at temperatures below 300.degree. C for long periods of time.
In order to avoid the unfavorable side reactions, it is necessary, therefore, to heat the reaction mixture rapidly to the reaction temperature. This may be accomplished by providing sufficient heating surface, which is, however, almost impossible in the industrial production of estrone. Consequently, a solution to this problem would be most desirable.